Myositis as a neuromuscular complication of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICI) induce improved clinical outcomes associated with numerous cancers, but immune-related adverse events can occur, including neuromuscular complications. We searched for all muscle biopsies from the patient data system of University Hospitals Leuven (UZ Leuven) from January 2014 to July 2018 (n = 686) and collected clinical data of patients with a biopsy-proven ICI-related myositis and expanded the pathological examinations. We identified three cases of ICI-related myositis in patients with malignant melanoma. The clinical phenotype ranged from mild to life threatening. Two patients had a myositis-myasthenia gravis overlap syndrome and one had a co-occurring myocarditis. Pathological examination showed a necrotizing and/or inflammatory myopathy with CD4 + and CD8 + T cells and CD68 + macrophages. IgG staining was positive in all cases. PD-1 and PD-L1 reactions were negative for inhibitors of the PD-1/PD-L1 pathway (nivolumab, atezolizumab) and positive for CTLA-4 inhibitors (ipilimumab). With increasing usage of ICI, clinicians must be aware of rare but potentially serious adverse events such as myositis. Early detection by inquiring about complaints and clinical signs of weakness and monitoring the creatine phosphokinase level in serum are recommended. Our histological findings are in line with other reports. The IgG positivity suggests a local role of the ICI in the pathophysiology of the myositis. Further research must be performed to identify patients at risk and to optimize treatment of the complications.